The long term goal of our studies is to elucidate the neuroendocrine mechanisms that underlife the ontogeny of gonadotropin secretion in higher primates, including man. In the present proposal we hope to gain an insight into the nature of the extra-gonadal mechanism responsible for the apparent restraint of hypothalamic GnRH secretion during the greater part of prepubertal development and, therefore, for the protracted delay in the onset of puberty in these species. Using the rhesus monkey as an experimental paradigm, we will address the view that the pubertal reactivation of the hypothalamic mechanism responsible for the pulsatile secretion of gonadotropin is triggered by a metabolic or humoral signal. We will determine the role, if any, of neurons sensitive to generalized CNS depression and of opioid neurons in maintaining the prepubertal restraint of gonadotropin secretion. We will complete our studies of the effects of neonatal adrenalectomy on the onteogeny of gonadotropin secretion. In addition, we propose to investigate the role of the fetal testis in determining the early ontogeny of the hypothalamic oscillator that generates the intermittent secretion of GnRH. Blood infusion-withdrawal devices that permit continuous access to the circulation of the rhesus monkey without restraint or anesthesia will be used to conduct servo-controlled cross circulation experiments, or chronically administer drugs and hormones, and to collect sequential blood samples. Routine sera-hematologic techniques will be employed in the cross cirulation experiments to match blood types and to monitor anticoagulation therapy. Hormone concentrations in plasma will be determined by established radioimmunoassay procedures and pulsatile patterns of LH and FSH secretion will be analyzed by computer executed algorithms. The aim of the studies described in the present proposal is to provide the initial insight into the mechanism responsible for the protracted delay in the onset of puberty in man, and thus provide the basis for further and systematic study of this fundamental problem in human development.